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Over the past decades, there has been a rapid increase in the incidence and prevalence of inflammatory bowel disease (IBD) in Asia. The natural history of IBD in Asian patients could be different from that in Western patients due to variations in disease phenotypes and genotypes as well as the healthcare environment between the 2 populations. To adequately cope with this disease, it is important to fully understand the potential differences in its natural history among different populations. In this review, we evaluated the differences in the clinical course of IBD between Asian and Western patients with regards to phenotypic progression, hospitalization, major surgery, risk of colorectal cancer, and mortality, mainly based on the results of population-based studies. The findings of our narrative review suggest that the clinical course of Asian patients with IBD, especially ulcerative colitis, is better than that of Western patients, as indicated by the lower rates of major surgery and hospitalization. In addition, similar to Western patients, the clinical course of Asian patients with IBD has been improving as evidenced by the decreasing rates of disease behavior progression (in Crohn’s disease), hospitalization, and major surgery.

Background: Despite recent advances in first-line chemotherapy for advanced pancreatic cancer, standard treatment after the failure of initial chemotherapy has not been established. Hence, we aimed to retrospectively analyze the clinical characteristics and outcomes of second-line chemotherapy in patients with advanced pancreatic cancer. Methods: We reviewed the clinical data of patients with advanced pancreatic cancer who underwent palliative chemotherapy at Kosin University Gospel Hospital between January 2013 and October 2020.Results: Among 366 patients with advanced pancreatic cancer who had received palliative chemotherapy, 104 (28.4%) underwent at least one cycle of second-line chemotherapy. The median age of the patients at the time of initiating second-line treatment was 62 years (interquartile range, 57–62 years), and 58.7% (61 patients) of them were male. The common second-line chemotherapy regimens were 5-fluorouracil (FU) plus leucovorin, irinotecan, and oxaliplatin (33 patients, 31.7%); gemcitabine/nab-paclitaxel (29, 27.9%), gemcitabine±erlotinib (13, 12.5%); and oxaliplatin and 5-FU/leucovorin (12, 11.5%). The median overall survival (OS) and progression-free survival were 6.4 months (95% confidence interval [CI], 4.5–8.6 months) and 4.5 months (95% CI, 2.7–6.3 months), respectively. In a multivariate analysis, poor performance status (PS) (hazard ratio [HR], 2.247; p=0.021), metastatic disease (HR, 2.745; p=0.011), and elevated carcinoembryonic antigen (CEA) levels (HR, 1.939; p=0.030) at the beginning of second-line chemotherapy were associated with poor OS.Conclusion: The survival outcome of second-line chemotherapy for advanced pancreatic cancer remains poor. However, PS, disease extent (locally advanced or metastatic), and CEA level may help determine patients who could benefit from second-line treatment.

The purpose of this study was to evaluate the impact of the different region-of-interest (ROI) methods of 2-D shear wave elastography (2-D SWE) on hepatic fibrosis diagnosis. In this retrospective study, 83 patients who underwent 2-D SWE with three ROI methods (a circle ROI, a box ROI and multiple ROIs in an elastogram) and transient elastography (TE) were included. Liver stiffness (LS) was measured five times with each ROI method. These LS values were compared, and their correlation with those obtained from TE was evaluated. The LS values obtained using the three different ROI methods differed statistically (p0.001). However, the LS values obtained using each ROI method of 2-D SWE were highly correlated with those obtained using TE (r0.7, p0.001). All three ROI methods of 2-D SWE had high areas under the receiver operating characteristic curve in diagnosing significant fibrosis and cirrhosis (0.841, 0.820 and 0.840, respectively; 0.962, 0.946 and 0.945, respectively). There were no significant differences in area under the receiver operating characteristic curve among the ROI methods of 2-D SWE. Regardless of the ROI method, 2-D SWE had high performance in diagnosing hepatic fibrosis.

Background The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. Methods This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. Results Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. Conclusions Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Objective Henoch–Schonlein purpura is a systemic vasculitis that mainly occurs in children. Renal impairment is a major complication of Henoch–Schonlein purpura, but there is no established predictive marker for renal involvement. Thus, in this study, we investigated the risk factors for renal involvement in children with Henoch–Schonlein purpura. Method The medical records of children newly diagnosed as having Henoch–Schonlein purpura between 2005 and 2020 were reviewed retrospectively. Selected laboratory data were recorded before treatment initiation. The date and the age at diagnosis; sex; and the presence of arthralgia, gastrointestinal and renal involvement were obtained retrospectively. Results This study included a total of 186 patients with Henoch–Schonlein purpura. Among them, 36.0% had renal involvement; 28.4% had only microscopic hematuria, 53.7% had non-nephrotic range proteinuria, and 17.9% had nephrotic-range proteinuria during follow-up. The mean age was higher (p = 0.016) and female sex was predominant (p = 0.001) in patients with renal involvement than in those without renal involvement. Blood neutrophil/lymphocyte ratio (p = 0.002) and platelet/lymphocyte ratio (p = 0.002) were significantly higher than that of the patients without renal involvement. No statistically significant differences were observed in the hemoglobin concentration, platelet count, presence of arthralgia, and gastrointestinal involvement between patients with and without renal involvement. Logistic regression analysis revealed female sex (odd ratio = 3.213) and neutrophil/lymphocyte ratio (odd ratio = 1.329) as risk factors for renal involvement. Conclusions Female sex and high neutrophil/lymphocyte ratio were risk factors for renal involvement in Henoch–Schonlein purpura.

BackgroundThis study aimed to classify the distinct group of patients with axial spondyloarthritis (SpA) on tumour necrosis factor alpha inhibitors (TNFi) according to the baseline characteristics using a clustering algorithm.MethodsThe clinical characteristics and demographic data of patients with axial SpA included in the Korean College of Rheumatology Biologics and Targeted Therapy registry were investigated. The patterns of disease manifestations were examined using divisive hierarchical cluster analysis. After clustering, we compared the clinical characteristics of patients and the drug survival of TNFi between the classified groups.ResultsA total of 1042 patients were analysed. The cluster analysis classified patients into two groups: axial group predominantly showing isolated axial manifestations (n= 828) and extra-axial group more frequently showing extra-axial symptoms (n= 214). Almost all extra-axial symptoms (peripheral arthritis, enthesitis, uveitis, and psoriasis) were more frequently observed in the extra-axial group than in the axial group. Moreover, patients in the extra-axial group had shorter disease duration, later disease onset, and higher disease activity than those in the axial group. The disease activity was comparable between the two groups after 1 year of treatment with TNFi. Interestingly, the extra-axial group had a lower drug survival with TNFi than the axial group (p= 0.001).ConclusionsCluster analysis of patients with axial SpA using TNFi classified two distinct clinical phenotypes. These clusters had different TNFi drug survival, clinical characteristics, and disease activity.

Background/Aims: Our study aimed to evaluate the long-term outcomes and risk factors for relapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established. Methods: A retrospective multicenter cohort study was conducted involving patients with Crohn’s disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued firstline anti-TNF therapy after achieving clinical remission. Results: A total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56 months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Cox analysis revealed that discontinuation owing to the clinician’s decision was associated with lower risk of relapse (vs patient’s preference: hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab: HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing: HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient’s preference (n=6), and other factors (n=4). Conclusions: More than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response. (Gut Liver 2021;15:752-762)

Rationale: Exposure to humidifier disinfectants (HDs) can increase the risk of asthma, but the characteristics of HD-related asthma are currently unclear. Polyhexamethylene guanidine (PHMG)–contain...

Purpose: The first-line antithyroid drug for children and adolescents with Graves’ disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment.Methods: We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: 0.7 mg/kg/day (group C; n=28).Results: The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively).Conclusion: The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.

Background: Stroke is one of the leading causes of death and disability in adulthood worldwide. A simple and convenient diagnostic method is needed for monitoring high-risk patients for stroke. Few POCTs are available for stroke diagnosis. Soluble blood P-selectin is known as a biomarker for platelet aggregation. Increased expression of P-selectin is observed in coronary artery disease, acute myocardial infarction, stroke and peripheral arterial disease. Objective: A simple method that can measure the increased expression of P-selectin in stroke patients is intended to be used for diagnosis or early detection and hospital monitoring of ischemic stroke. Method: Plasma proteins in blood were separated using a three-layered filter system. Quantum dot and antibody were conjugated to detect biomarkers present in plasma and then measured with a fluorescence spectrophotometer. Results: The detection limit of soluble P-selectin confirmed by immunoassay was 1 ng/ul. In order to increase the sensitivity and simplify the reaction, the detection limit was measured to evaluate the sensitivity of the quantum dot labeled anti P-selectin antibody. As a result, P-selectin of 5 ng/ul or more showed saturation signal intensity, indicating the upper limit of detection, and 10 pg/ul was the lower limit of detection. Conclusion: In this study, we proposed a three-layer filter membrane system that can separate biomarker- rich fractions from whole blood, simplifying the analysis process and improving sensitivity by using quantum dot-labeled antibodies to detect biomarkers. We hope that our system complements the advantages of POCT and can be applied to real clinical applications.

The biomarkers and therapeutic targets of neutrophilic asthma (NA) are poorly understood. Although S100 calcium-binding protein A9 (S100A9) has been shown to correlate with neutrophil activation, its role in asthma pathogenesis has not been clarified. This study investigated the mechanism by which S100A9 is involved in neutrophil activation, neutrophil extracellular trap (NET)-induced airway inflammation, and macrophage polarization in NA. The S100A9 levels (by ELISA) in sera/culture supernatant of peripheral blood neutrophils (PBNs) and M0 macrophages from asthmatic patients were measured and compared to those of healthy controls (HCs). The function of S100A9 was evaluated using airway epithelial cells (AECs) and PBNs/M0 macrophages from asthmatic patients, as well as a mouse asthma model. The serum levels of S100A9 were higher in NA patients than in non-NA patients, and there was a positive correlation between serum S100A9 levels and sputum neutrophil counts (r = 0.340, P = 0.005). Asthmatic patients with higher S100A9 levels had lower PC20 methacholine values and a higher prevalence of severe asthma (SA) (P, S100A9 as a biomarker for neutorphilic asthma A calcium-binding protein called S100A9 could be used as a biomarker for diagnosing a phenotype of asthma called neutrophilic asthma, and might also be a suitable target for drugs to treat the condition. Hae-Sim Park and colleagues at Ajou University in Suwon, South Korea, investigated the mechanism by which S100A9 activates neutrophils to induce the airway inflammation and other changes associated with asthma. Patients with neutrophilic asthma had higher levels of the protein in their blood. Measuring these levels could therefore be used as a potential biomarker. Serum biomarkers for identifying neutrophilic asthma are currently lacking. The research also supports the hypothesis that S100A9 plays a critical role in initiating and perpetuating the neutrophilic asthma and could become the therapeutic target.

Purpose: To assess characteristics the application of mobile medication system and medication administration error (MAE) alerts in a general hospital.Methods: The subject hospital adopted a mobile medication system in 2016. All medication administrations in the general wards and ICUs were automatically recorded in real-time using identification barcodes, drug barcodes, and hand-held point-of-care devices. MAE alert logs were recorded from April 1st 2017 to March 31st 2018. For this study analysis was done using Pearson’s chi-squared test for potentially related factors of MAE alerts included administration time, order type, medication route, and length of nurse’s employment.Results: The total number of medications during the period of this study was 3,227,990. Among them, 2,698,317 medication doses were recorded, resulting in the system application rate of 83.6%. The system application rate was significantly correlated with all factors related to potential MAE alters. In this study 23,314 MAE alerts(0.9% of the total medication doses) were identified. The MAE alerts were related to new (OR=2.26, p

Background This study aimed to evaluate the association between the high risk of cardiovascular disease (CVD) and the consumption of sugar-sweetened beverages (SSBs) in Korean men. Methods This cross-sectional study analyzed the data of 3,705 men (age 30-64 years) who participated in the 2014-2016 Korea National Health and Nutrition Examination Survey (KNHANES). SSB intake was defined as the sum of the intakes of carbonated beverages and fruit juices. Participants were categorized into study groups depending on their intake of SSBs: ≤2, 3-4, or ≥5 times per week. High CVD risk was defined as a 10-year risk of more than 10%, based on the Framingham Heart Study 10-year CVD Risk Calculator. The association between high CVD risk and SSB intake was evaluated using a multivariable-adjusted logistic regression model. Results Korean men who consumed SSBs 3-4 and ≥5 times a week showed a multivariate-adjusted odds ratio of 1.49 (95% confidence interval [CI], 1.05-2.11) and 1.61 (95% CI, 0.97-2.67) for high CVD risk, respectively, compared with those who consumed SSBs ≤2 times per week. Additionally, the risk of CVD increased with the increase in the intake of SSBs (P-trend=0.01). In subgroup analysis, no association was observed between SSB intake and high CVD risk in the group with regular physical activity (P for interaction=0.01). Conclusion In Korean men, except those with regular physical activity, SSB intake ≥3 times a week is associated with a high risk for CVD (10-year CVD risk ≥10%).

Background: Fractional picosecond lasers is effective for the treatment of wrinkles or acne scars. Objective: To investigate the safety and efficacy of treatment with a fractional 1,064-nm picosecond laser with a diffractive optic element for facial wrinkles and acne scars. Methods: This prospective open-labeled trial comprised 22 subjects with facial wrinkles or acne scars. Subjects received three laser treatments with a fractional 1,064-nm picosecond laser at 3-week intervals. The efficacy and safety were evaluated at every visit and 2 months after the final treatment (14 weeks from the first treatment session). Global photographic assessments were performed by three blinded dermatologists and the subjects. Skin profilometry was performed using three-dimensional digital photographs; viscoelasticity was measured. Results: The overall mean global improvement scores assessed by the dermatologists at weeks 3, 6, and 14, were 1.8±1.46, 2.5±1.88, and 3.5±1.84, respectively, and those assessed by the subjects were 2.7±2.08, 4.1±2.24, and 5.0±2.52, respectively. Skin profilometry showed significant improvements in the skin wrinkles, texture, depressions, and pores. The gross elasticity and skin firmness significantly improved by 10.96% and 9.04%, respectively. The major adverse reactions were erythema, pruritus, and petechiae, which disappeared within 2∼3 days. Conclusion: The fractional 1,064-nm picosecond laser is an effective and safe therapeutic modality for skin rejuvenation. (Ann Dermatol 33(3) 254∼262, 2021)

BACKGROUND AND AIM Data comparing the outcomes of cyclosporin A (CsA) and infliximab (IFX) as rescue therapy for steroid-refractory acute severe ulcerative colitis (SR-ASUC) among Asians are scarce. METHODS In this single-center study, we retrospectively reviewed 121 patients with SR-ASUC according to the Truelove and Witts' criteria who received CsA or IFX as rescue therapy between 1995 and 2015. The cumulative rates of treatment failure and colectomy at 3 months were compared. Treatment failure was defined as colectomy, switch to other medications, acute flare-up events requiring steroid treatment, or adverse events leading to drug interruption. RESULTS Among 121 patients with SR-ASUC (male, 55.6%; median disease duration, 47.1 months; extensive colitis, 61.2%), 23 received CsA as rescue therapy. Baseline characteristics (e.g. age at diagnosis, sex, disease duration, disease extent at rescue therapy, and Mayo score at treatment initiation) were comparable between the two groups. During follow-up (median, 45 months; interquartile range 29.3-61.8), 84 patients (69.4%) experienced treatment failure, and 25 patients (20.7%) underwent colectomy. The CsA group and the IFX group did not show significant differences in the cumulative rates of treatment failure (39.1% vs 34.7%, P = 0.714) and colectomy (26.1% vs 13.3%, P = 0.198) at 3 months. Previous use of azathioprine (odds ratio [OR] = 2.309, 95% confidence interval [CI] = 1.076-4.951, P = 0.032) was associated with treatment failure at 3 months. Mayo score > 10 at the time of rescue therapy was significantly associated with colectomy at 3 months (OR = 8.444, 95% CI = 2.592-27.506, P

The purpose of this study is to identify the research trend of innovation capacity and technological innovation that are recently required in companies. This was done by collecting and analyzing dissertation abstracts from Springer and Scopus, which are websites with a collection of dissertations. For the research method, this study used NetMiner 4 and R program for text data analysis amongst unstructured data analysis, and analysis methods like keyword network analysis, LDA, and TreeMap were applied. The analysis results showed that there is a difference in the importance of technological innovation and absorptive capacity of Springer and Scopus

Objective. Ankylosing spondylitis (AS) is a chronic inflammatory disease with obvious male preponderance. Males show more severe radiographic manifestations compared with females. This study aimed to evaluate the effects of sex and estrogen on the radiographic progression of AS. Methods. A total of 101 patients with AS were included in this study. All of the radiographs were scored using the modified Stoke AS Spine Score (mSASSS). Serum levels of 17β-estradiol (E2), dickkopf-1 (Dkk1), and leptin were detected by enzyme-linked immunosorbent assay. The generalized estimating equations model was used to evaluate factors associated with spinal radiographic progression. Results. The mean age at disease onset was 27.3±10.7 years, and 16 patients (15.8%) were female. In the multivariable analysis, body mass index (β-coefficient=0.12; p=0.047) and levels of Dkk1 (β-coefficient=-0.11; p＜0.001), and female (β-coefficient=-1.40; p=0.001) were associated with radiographic progression. Among male patients with AS, baseline C-reactive protein (β=0.11; p=0.005) and mSASSS (β=0.21; p=0.030) were also associated with radiographic progression. E2 and leptin levels were not significantly related to the radiographic progression. Conclusion. Although female patients were associated with less radiographic progression in AS, there was no significant relationship between serum estrogen level and radiographic progression. Results of current study suggests that genetic factors or other environmental factors associated with female may influence radiographic progression in patients with AS. (J Rheum Dis 2021;28:76-84)

Background: The number of patients requiring dialysis is increasing worldwide, and the atrial fibrillation (AF) prevalence among hemodialysis (HD) patients is higher than in the general population. There have been no studies of Korean AF patients undergoing HD investigating how AF affects outcomes, for example, in terms of all-cause mortality, hospitalization, and stroke events. We conducted a large-scale retrospective cohort study with data from the National Health Insurance System (NHIS) to determine how AF affects these outcomes. Methods: In 2013, the Health Insurance Review and Assessment (HIRA) service, a Korean national health insurance scheme, collected data from 21,839 HD patients for evaluating the adequacy of dialysis centers. All-cause mortality, hospitalization, and stroke events were compared between patients with and without AF. Sub-analyses compared these outcomes between patients receiving and not receiving warfarin. Results: Cox regression analysis found that AF was a significant risk factor for death from any cause (HR, 1.356; 95% CI, 1.222-1.506, P < 0.001), hospitalization (HR, 1.323; 95% CI, 1.225-1.430, P < 0.001), and hemorrhagic stroke (HR, 1.500; 95% CI, 1.050-2.141, P = 0.026). AF was not significantly associated with an increased risk of ischemic stroke. The use of warfarin was significantly associated with hemorrhagic stroke incidence (HR, 1.593; 95% CI, 1.075-2.360, P = 0.020), while there was no significant correlation between warfarin treatment and all-cause mortality, hospitalization, and ischemic stroke. Conclusions: This cohort study of Korean dialysis patients showed that AF was a risk factor for multiple outcomes among HD patients.

Although upper gastrointestinal (GI) neoplasms are not rare in patients with familial adenomatous polyposis (FAP), few studies have focused on them and the long-term outcomes of their treatment by endoscopy. Therefore, we aimed to investigate the prevalence and endoscopic treatment outcomes of upper GI neoplasms in patients with FAP. Among 215 patients diagnosed with FAP between January 1991 and December 2019, 208 who underwent esophagogastroduodenoscopy were eligible. The clinical features and endoscopic treatment outcomes of upper GI neoplasms were retrospectively investigated and analyzed. Among the enrolled patients, 113 (54.3%) had one or more upper GI neoplasms: gastric adenoma (n = 34), gastric cancer (n = 7), nonampullary duodenal adenoma (n = 86), and ampullary adenoma (n = 53). Among patients with gastric neoplasms (n = 37), 24 (64.9%) underwent treatment (endoscopic treatment: 22, surgery: 2). No tumor-related mortality occurred during median follow-up of 106 months (interquartile range [IQR] 63–174). Endoscopic treatment was performed in 47 (54.7%) of 86 patients with nonampullary duodenal adenoma and in 32 (60.4%) of 53 patients with ampullary adenoma. No patient underwent surgery for duodenal neoplasms, and no tumor-related mortality occurred during median follow-up of 88 months (IQR 42–145). The proportion of patients with increased Spigelman stage at 2 years after the initial diagnosis or treatment was significantly higher in untreated group than in the group treated for duodenal neoplasms (27.3% vs. 0.0%, p = 0.001). Endoscopic surveillance in FAP patients is important for the detection and treatment of upper GI neoplasms in early stage. In particular, endoscopic therapy for duodenal neoplasms can reduce the severity of duodenal polyposis.

Background: While atypical antipsychotic medications are widely used for treating depressive disorders, their long-term effects on the risk of subsequent dementia have not been studied adequately. Objective: To investigate whether the risk of dementia differs according to the use of atypical antipsychotic drugs, and compare the effects of antipsychotic agents on dementia risk in individuals with late-life depressive disorders. Methods: A nationwide population-based retrospective cohort study was conducted using data from the National Health Insurance Service—Senior Cohort of South Korea. Atypical antipsychotic dosages were standardized using a defined daily dose, and the cumulative dosage was calculated. Participants were observed from January 2008 to December 2015. Cox proportional hazard regression analysis was used to estimate the hazard ratios. Results: The cohort included 43,788 elderly adults with depressive disorders: 9,901 participants (22.6%) were diagnosed with dementia. Findings showed that atypical antipsychotics were prescribed to 1,967 participants (4.5%). Compared with non-users, users of atypical antipsychotics experienced a significantly higher risk for dementia with an adjusted hazard ratio (aHR) of 1.541 (95% confidence interval [CI], 1.415–1.678). A cumulative dose-response relationship was observed (test for trend, p

Backgrounds/aims PPARγ, farnesoid X receptor (FXR) and CYP7A1 are associated with solubility of bile. This study was performed to understand a mechanism and interactions of statin-induced PPARγ, PGC-1α and HNF-4α related to the statin-induced activation of FXR and CYP7A1, and verify whether the mevalonate pathway is involved in the mechanism. Methods MTT assays were performed using cultured human Hep3B cells to determine the effect of atorvastatin on the cell proliferation. Expression levels of indicated proteins were measured using Western blotting assays by inhibiting the protein expression or not. Results Atorvastatin increased expression of PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. PPARγ ligand of troglitazone upregulated the expression of PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. Silencing of PPARγ, PGC1α, and HNF4α using respective siRNA demonstrated that atorvastatin-induced FXR and CYP7A1 activation required sequential action of PPARγ /PGC-1α/HNF-4α. The silencing of PPARγ completely inhibited atorvastatin-induced PGC-1α expression, and the PGC1α silencing partially inhibited atorvastatin-induced PPARγ expression. The inhibition of HNF4α did not affect atorvastatin-induced PPARγ expression, but partially inhibited atorvastatin-induced PGC-1α expression. Besides, mevalonate completely reversed the effect of atorvastatin on PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1. Conclusions Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.

Background: Prognosis of patients with HER-2 positive metastatic breast cancer (MBC) has been revolutionized with the development of dual antibodies targeting HER-2 and antibody-drug conjugate, but resistance to anti-HER-2 therapy is inevitable ultimately. PI3K-AKT-mTOR pathway aberration is known to be one of the resistance mechanisms. This randomized phase 2 pilot study evaluated safety and efficacy of Herzuma® (trastuzumab biosimilar) plus Gedatolisib (dual PI3K/mTORC inhibitor) in patients with HER-2 positive MBC who progressed after multiple lines of therapy. Methods: Patients with HER-2 positive MBC with known PIK3CA pathologic mutation or amplification whose disease progressed after more than two HER-2 directed therapy were enrolled in the study. They received Herzuma® (8mg/kg IV for 1st cycle loading dose, and then 6mg/kg IV every 3 weeks) plus Gedatolisib (180mg on D1, 8, 15 of every 21 days). We evaluated efficacy of the combination treatment as interim analysis. The data cutoff of this interim analysis was Aug 4, 2020. Results: As a pilot study, 15 patients were enrolled and followed for a median of 2.3 months. At data cutoff, 11 patients were eligible for response assessment. All patients were confirmed to have pathologic PIK3CA aberrations: H1047R, H1047L, E542Q, E542K, E453K, N345K, and PIK3CA amplification. Five patients reached partial response (PR) as their best response, three were stable disease (SD), and three had progressive disease (PD). All patients who have reached PR remain on investigational treatment at the data cutoff point, and the longest one is on treatment for 7.8 months. One of the SD patients ended treatment due to disease progression, and the other two have been undergoing treatment. Overall, response rate was 45.5% and disease control rate was 72.7%. No fatal adverse events related to trial medication were reported. Conclusion: In this phase 2 pilot study, Trastuzumab biosimilar plus Gedatolisib presented 45.5% of response rate with manageable toxicity in patients with HER-2 positive MBC with PIK3CA aberration. Clinical trial information: NCT03698383 Acknowledgement: this research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (Grant number: HI17C2206). Citation Format: Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong Won Lee, Keon Uk Park, Eun Mi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Mi So Kim, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, In Hae Park, Kyong Hwa Park. Phase II pilot study of trastuzumab biosimilar (herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis] [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-39.

5-Fluorouracil (5-FU) is an essential drug in systemic chemotherapy treatments for colorectal cancer (CRC). Despite the development of several treatment strategies over the past decades, the patient benefits of 5-FU-based therapies have been compromised by the development of chemoresistance. Differences in treatment responses among CRC patients may be due to genetic and epigenetic factors unique to individuals. Therefore, important factors for realizing personalized medicine are to accurately understand the causes and mechanisms of drug resistance to 5-FU-based therapies and to identify and validate prognostic biomarkers. Gut microbes that interact directly with the host contribute to human health and cancer control. Lactobacillus plantarum, in particular, has the potential to be a therapeutic agent by producing bioactive compounds that may benefit the host. Here, we investigated the gamma-aminobutyric acid (GABA) and GABAB receptor (GABABR)-dependent signaling pathway as a treatment option for 5-FU-resistant HT-29 cells. GABA-producing L. plantarum activates anti-proliferative, anti-migration, and anti-invasion effects against 5-FU-resistant HT-29 cells. The inhibitory effects of GABA-producing L. plantarum are mediated via GABABR. Activated GABABR induces apoptosis through the inhibition of cAMP-dependent signaling pathways and cellular inhibitor of apoptosis protein 2 (cIAP2) expression. Thus, the GABAergic system has potential in 5-FU-resistant HT-29 cells as a predictive biomarker. In addition, GABA-producing L. plantarum is promising as an adjuvant treatment for 5-FU-resistant CRC, and its intervention in neurobiological signaling imply new possibilities for chemoprevention and the treatment of colon cancer-related diseases.

Malnutrition after gastrectomy is associated with a poor prognosis; however, no accurate model for predicting post-gastrectomy malnutrition exists. Hence, we conducted a retrospective study to develop a prediction model identifying gastric cancer patients at high risk of malnutrition after gastrectomy. Gastric cancer patients who underwent curative gastrectomy with more than one weight measurement during a 3-year follow-up period were included. Malnutrition was defined as body mass index (BMI)

Sialolithiasis is one of the most common causes of salivary duct obstruction. In the last 20 years, minimally invasive procedures like sialendoscopy, extracorporeal lithotripsy, and basket snaring are increasingly being used for the treatment of salivary gland duct stones. Sialo-irrigation of the salivary gland is an effective procedure for treating inflammation and providing symptomatic relief. This procedure can be employed for the treatment of sialolithiasis using the back pressure of instilled saline. Sialo-irrigation under ultrasound (US) guidance allows for dynamic studies showing real-time images during diagnostic or surgical procedure and can be used for the removal of sialoliths. In addition, it can also be used to remove primitive sialoliths and microliths by washing out the ductal system, which prevents the recurrence of sialoliths. The aim of this study was to propose a minimally invasive technique for sialolithiasis using US-guided sialo-irrigation.

Background: E-cigarettes are steadily gaining popularity in Korea. However, the characteristics of e-cigarette smokers, especially nicotine dependence and stress susceptibility, have not been evaluated in comparison to those of nonsmokers or combustible cigarette smokers in Korea. Methods: In this study, 28,059 participants from the Korea National Health and Nutrition Examination Survey (2013-2017) were classified into the following three groups: non-smokers, smokers (current smokers and ex-smokers of combustible cigarettes only), and e-smokers (current smokers and ex-smokers of e-cigarettes regardless of combustible cigarette use). Results: Among the participants, 16,980 (60.5%), 9,247 (33.0%), and 1,832 (6.4%) subjects were non-smokers, smokers, and e-smokers, respectively. E-smokers were younger, more educated, and had a higher household income than nonsmokers or smokers. The number of e-smokers who smoked within 5 minutes of waking up (31.5% vs. 19.8%, p

Introduction: Chronic spontaneous urticaria (CSU) is a common cutaneous disease caused by mast-cell degranulation. Human β-defensin 2 (HBD2) is a well-known antimicrobial peptide that is also a pruritogen inducing vascular permeability via non-IgE-mediated mast-cell degranulation. Objective: We investigated the associations between serum HBD2 levels and the clinical characteristics of CSU patients. Methods: Serum samples from 124 CSU patients and 56 healthy controls were screened for the levels of HBD2 and translationally controlled tumor protein (TCTP)_ by using ELISA. The urticaria activity score over 7 days (UAS7) was used to measure disease activity in CSU patients. Accompanying angioedema was self-reported. Results: Serum HBD2 levels were higher in the CSU group than in healthy subjects (median [interquartile range], 84.1 [43.5, 142.5] vs. 59.5 [26.7, 121.5], p = 0.034). In CSU patients, serum HBD2 level was negatively correlated with the peripheral basophil percentages (Spearman’s rho = −0.229, p = 0.01) and vitamin D levels (−0.262, p = 0.02), but positively correlated with TCTP levels (0.252, p = 0.006). In CSU patients, HBD2 level was higher in those with than without angioedema (101.7 [50.9, 184.2] vs. 66.7 [37.9, 132.0], p = 0.019). It did not differ by aspirin hypersensitivity or atopy status, or autologous serum skin test positivity. Conclusion: A known mast-cell degranulator, HBD2 was elevated in the sera from CSU patients compared to healthy controls and may be involved in the pathogenesis of accompanying angioedema.

Liposomes, with their flexible physicochemical and biophysical properties, continue to be studied as an important potential a critical drug delivery system. Liposomes have overcome the challenges of conventional free drug therapy by encapsulating therapeutic agents, thereby improving in vivo biodistribution and reducing systemic toxicity. New imaging modalities and interpretation techniques, as well as new techniques for targetable system formulation technique, and tumor environmental information, have affected the search for a means of overcoming the difficulties of conventional liposome formulation. In this review, we briefly discuss how liposomal formulation has been applied across the biomedical field, particularly as a therapy, and the role it may play in the future, when paired with new developments in diagnosis and theranostics. The biological challenges that still remain and the translational obstacles are discussed.

The total iron level in the brain increases with age, and excess iron is associated with neurodegenerative diseases; however, the mechanism of brain iron deposition is unknown. In peripheral cells, the expression of hepcidin, a master regulator of iron homeostasis, is regulated by estrogen. This study aimed to determine whether hepcidin was involved in iron deposition in the brain and brain endothelial cells of estrogen-deficient aged female mice. Aged mice showed increased levels of hepcidin and ferritin in the brain and brain microvessels compared with young mice, and these levels were reduced by estrogen replacement in ovariectomized aged mice. In the brain endothelial cell line bEnd.3, the lipopolysaccharide (10 ng/mL)-induced increases of hepcidin mRNA and protein levels, the number of Prussian blue–positive cells, and free radicals were reduced after estrogen treatment. These results suggest that estrogen deficiency with an increase of hepcidin is partly responsible for iron deposition in the brain and brain endothelial cells and that hepcidin can be a target to prevent brain aging and neurodegeneration in postmenopausal women.

To assess the incidence and clinical characteristics of acute kidney injury (AKI) and identify the associated risk factors for AKI in children with type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA). This was a retrospective study performed over 15 y in a single Korean center. Children aged ≤18-y-old with T1DM and DKA were enrolled and divided into 2 groups according to the presence of AKI. This study included 90 episodes of DKA in 58 children with T1DM. AKI occurred in a total of 70 hospitalizations (77.8%) of 44 children: 18 (20.0%) with stage 1 AKI, 39 (43.3%) with stage 2 AKI, and 13 (14.4%) with stage 3 AKI. The number of AKI decreased to 28 (47.4%) and 13 (28.3%) after 12 h and 24 h of admission, respectively. The white blood cell count (P = 0.001) and anion gap levels (P = 0.025) were significantly higher and serum bicarbonate level (P = 0.004) was lower in the AKI group. Logistic regression analysis revealed that a longer duration of TIDM and high anion gap were independent predictors of developing severe AKI in pediatric DKA with T1DM (odds ratio, 1.225, P = 0.013; odds ratio, 1.130, P = 0.038). AKI frequently occurred in TIDM children with DKA. Longer duration of TIDM and elevated anion gap are associated with occurrence of severe AKI.

BACKGROUND AND AIM The clinical impact of perianal Crohn's disease (CD) (pCD), a well-known poor prognostic factor of CD, has not been fully evaluated in Asian patients. We investigated the outcomes of CD in Korean patients according to the presence of pCD at CD diagnosis. METHODS Using 2010-2014 data from the national health insurance claims database, we evaluated the disease course of CD according to the presence of pCD at CD diagnosis. The results were verified in a hospital-based cohort of 2923 patients. RESULTS The cumulative risk of intestinal resection was lower in patients with pCD at diagnosis than in those without, in the population-based cohort (9.1% vs 14.7% at 5 years after diagnosis, P

Excessive daytime sleepiness (EDS) is the most common symptom of sleep-disorders. Although high levels of EDS have been reported among firefighters, there is a limited understanding on EDS in firefighters. A cross-sectional survey was conducted in full-time firefighters (

Background Tofacitinib is a small molecule which inhibits janus kinase and has been shown to be effective for patients with active ulcerative colitis (UC). We investigated the real-life therapeutic effectiveness and safety of tofacitinib treatment for Korean patient with UC. Methods We retrospectively analyzed the data of patients with UC who received tofacitinib treatment at 10 hospitals in Korea. The primary outcome was clinical remission at week 16 which was defined as a partial Mayo score ≤2 with a combined rectal bleeding subscore and stool frequency subscore ≤1. The secondary outcome was endoscopic remission (Mayo endoscopic subscore ≤1) at week 16. Adverse events including herpes zoster and deep vein thrombosis were also evaluated. Results Between January 2018 and November 2020, a total of 123 patients with UC received tofacitinib treatment (Table 1). Clinical effectiveness was evaluated for those who had completed or stopped the tofacitinib therapy by week 16, week 24 and week 52, respectively (Figure 1). Clinical remission and response rates at week 16 were 65.3% and 73.7%, respectively (Figure 2A). Ninety-one out of 123 patients (74.0%) were followed up to week 52. Their clinical remission and response rates at week 52 were 49.5% and 58.2%, respectively (Figure 2A). Among 117 patients with baseline Mayo endoscopic subscore ≥2, endoscopic remission rate at week 16 was 55.6% (Figure 2C). Any adverse events occurred in 15 patients (12.2%) and serious adverse events occurred in 9 patients (7.3%). Herpes zoster occurred in 4 patients (3.3%) and one patient (0.8%) suffered from deep vein thrombosis (Table 2). Conclusion Tofacitinib was effective with an acceptable safety profile for Korean patients with UC in the real world.

Background The purpose of this study is to assess whether the application of preoperative forced air warming set to high temperature (> 43 °C) for brief period can increase temperature on admission to the postanesthesia care unit (PACU) and prevent hypothermia or shivering during holmium laser enucleation of the prostate performed under spinal anesthesia. Methods Fifty patients were enrolled were assigned randomly to receive passive insulation (control group, n = 25) or forced-air skin surface warming for 20 min before spinal anesthesia (pre-warming group, n = 25). The primary outcome was temperature at PACU admission. Results The pre-warming group had a significantly higher temperature on admission to the PACU than the control group (35.9 °C [0.1] vs 35.6 °C [0.1], P = 0.023; 95% confidence interval of mean difference, 0.1 °C–0.5 °C). The trend of decreasing core temperature intraoperatively was not different between groups (P = 0.237), but intraoperative core temperature remained approximately 0.2 °C higher in the pre-warming group (P = 0.005). The incidence of hypothermia on admission to the PACU was significantly lower in the pre-warming group (56% vs 88%, P = 0.025). Shivering occurred in 14 patients in the control group, and 4 patients in the pre-warming group (P = 0.007). Conclusion Brief pre-warming at 45 °C increased perioperative temperature and decreased the incidence of hypothermia and shivering. However, it was not sufficient to modify the decline of intraoperative core temperature or completely prevent hypothermia and shivering. Continuing pre-warming to immediately before induction of spinal anesthesia or combining pre-warming with intraoperative active warming may be necessary to produce clearer thermal benefits in this surgical population. Trial registration This trial was registered with Clinicaltrials.gov, NCT03184506, 5th June 2017.

The aim of the present study is to identify influential factors of travel intention under the context of highly developed IT society today. Due to the development of IT and diversified ways of technology convergence, individual travelers become highly efficient in travel-related information processing. As predicted, the results of both Korean and Chinese samples show that acquaintance recommendation, autonomy, relatedness, and technology self-efficacy are significantly related with the travel information acquisition and travel intention. In this study, smartPLS, which is widely used in social science, was used. PLS is a useful analytical tool for determining causality between variables. The present study will make practical contributions by enhancing the accuracy of travel recommendation services from the perspective of technology convergence. The results of this study are expected to provide guidelines for travel-related companies to develop personalization and customization services through big data and artificial intelligence techniques when they want to design travel recommendation systems.

Nonalcoholic fatty liver disease is a chronic condition involving steatosis, steatohepatitis and fibrosis, and its progression remains unclear. Although the tetraspanin transmembrane 4 L six family member 5 (TM4SF5) is involved in hepatic fibrosis and cancer, its role in nonalcoholic steatohepatitis (NASH) progression is unknown. We investigated the contribution of TM4SF5 to liver pathology using transgenic and KO mice, diet- or drug-treated mice, in vitro primary cells, and in human tissue. TM4SF5-overexpressing mice exhibited nonalcoholic steatosis and NASH in an age-dependent manner. Initially, TM4SF5-positive hepatocytes and liver tissue exhibited lipid accumulation, decreased Sirtuin 1 (SIRT1), increased sterol regulatory-element binding proteins (SREBPs) and inactive STAT3 via suppressor of cytokine signaling (SOCS)1/3 upregulation. In older mice, TM4SF5 promoted inflammatory factor induction, SIRT1 expression and STAT3 activity, but did not change SOCS or SREBP levels, leading to active STAT3-mediated ECM production for NASH progression. A TM4SF5-associated increase in chemokines promoted SIRT1 expression and progression to NASH with fibrosis. Suppression of the chemokine CCL20 reduced immune cell infiltration and ECM production. Liver tissue from high-fat diet- or CCl4 -treated mice and human patients exhibited TM4SF5-dependent steatotic or steatohepatitic livers with links between TM4SF5-mediated SIRT1 modulation and SREBP or SOCS/STAT3 signaling axes. TM4SF5-mediated STAT3 activation in fibrotic NASH livers increased collagen I and laminin γ2. Both collagen I α1 and laminin γ2 suppression resulted in reduced SIRT1 and active STAT3, but no change in SREBP1 or SOCS, and abolished CCl4 -mediated mouse liver damage. TM4SF5-mediated signaling pathways that involve SIRT1, SREBPs and SOCS/STAT3 promoted progression to NASH. Therefore, TM4SF5 and its downstream effectors may be promising therapeutic targets to treat nonalcoholic fatty liver disease. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.